Journal article

Recurrent SPECC1L-NTRK fusions in pediatric sarcoma and brain tumors

Dong-Anh Khuong-Quang, Lauren M Brown, Marie Wong, Chelsea Mayoh, Alexandra Sexton-Oates, Amit Kumar, Mark Pinese, Sumanth Nagabushan, Loretta Lau, Louise E Ludlow, Andrew J Gifford, Michael Rodriguez, Jayesh Desai, Stephen B Fox, Michelle Haber, David S Ziegler, Jordan R Hansford, Glenn M Marshall, Mark J Cowley, Paul G Ekert

Cold Spring Harbor molecular case studies | COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT | Published : 2020


The identification of rearrangements driving expression of neurotrophic receptor tyrosine kinase (NTRK) family kinases in tumors has become critically important because of the availability of effective, specific inhibitor drugs. Whole-genome sequencing (WGS) combined with RNA sequencing (RNA-seq) can identify novel and recurrent expressed fusions. Here we describe three SPECC1L-NTRK fusions identified in two pediatric central nervous system cancers and an extracranial solid tumor using WGS and RNA-seq. These fusions arose either through a simple balanced rearrangement or in the context of a complex chromoplexy event. We cloned the SPECC1L-NTRK2 fusion directly from a patient sample and showe..

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Awarded by National Health and Medical Research Council (NHMRC)

Awarded by NHMRC

Awarded by Cancer Australia

Funding Acknowledgements

iPredict is a Flagship project of Melbourne Genomics and funded by the State Government of Victoria (Department of Health and Human Services) and the 10 member organizations of the Melbourne Genomics Health Alliance. S.B.F. acknowledges the support of the National Health and Medical Research Council (NHMRC) Grant Funding APP1079329. P.G.E. acknowledges the support of NHMRC Project Grant APP1140626, the Samuel Nissen Charitable Foundation, and the Steven Walter Children's Cancer Foundation. G.M.M. acknowledges the support of Hyundai 4K and Steven Walter Children's Cancer Foundation. Zero is a national study of precision medicine in pediatric cancer supported by the Australian Federal Government Department of Health, New South Wales State Government, the Australian Cancer Research Foundation (ACRF), The Kids Cancer Alliance, Cancer Therapeutics Cooperative Research Centre (CTx CRC), Tour de Cure (tumor biobank personnel), Lions Kids Cancer Genome Project (WGS and personnel), Cure Brain Cancer Foundation, The Kids Cancer Project, University of New South Wales, Australian Genomics Health Alliance, Luminesce Alliance, The Medical Research Future Fund (MRFF) Australian Brain Cancer Mission, Minderoo Foundation's Eliminate Cancer Initiative, Zero Childhood Cancer Capacity Campaign, The Kinghorn Foundation, the Cancer Institute NSW, and NSW Health (Fellowship funding for M.J.C.). Cancer Australia provided personnel and computational support (APP1165556 to M.J.C.). Zero Childhood Cancer is a joint initiative led by Children's Cancer Institute and Sydney Children's Hospital Randwick.